Abstract: BACKGROUND: In 2010, there were approximately 2.2 million emergency room visits associated with traumatic brain injury (TBI), with 80 percent diagnosed as mild TBI or concussion. In addition, there are a large number of TBIs, especially mild TBIs, which go either unreported by patients or initially undiagnosed by clinicians. Our team has previously identified a panel of immune-related genes that can diagnose ischemic stroke at triage, and due to shared pathophysiological mechanisms of TBI and stroke, we hypothesized that this panel of genes may also be utilized for the diagnosis of TBI. OBJECTIVES: The primary aims of this pilot study were to: (1) characterize changes in a panel of immune-related genes in TBI; (2) identify immune-related biomarkers that may be used to diagnose TBI and (3) describe the peripheral immune response following TBI. METHODS: Blood was drawn from TBI patients no later than 24 h of injury onset and matched control subjects. Real-time PCR was used to measure gene expression, and a white blood cell differential was performed to obtain neutrophil and lymphocyte percentages. RESULTS: Relative mRNA expression of ARG1, LY96, MMP9, s100a12 was significantly increased and CCR7 was significantly decreased in peripheral blood of TBI patients within 24 hours of injury compared to control subjects. We also observed a different pattern of leukocyte dynamics following TBI between mild and severe TBI. CONCLUSIONS: We have described a panel of immune-related genes that can accurately predict/diagnose TBI with higher sensitivity and specificity of other biomarkers to date.